Lineage context switches the function of a C. elegans Pax6 homolog in determining a neuronal fate

Development. 2019 Apr 15;146(8):dev168153. doi: 10.1242/dev.168153.


The sensory nervous system of C. elegans comprises cells with varied molecular and functional characteristics, and is, therefore, a powerful model for understanding mechanisms that generate neuronal diversity. We report here that VAB-3, a C. elegans homolog of the homeodomain-containing protein Pax6, has opposing functions in regulating expression of a specific chemosensory fate. A homeodomain-only short isoform of VAB-3 is expressed in BAG chemosensory neurons, where it promotes gene expression and cell function. In other cells, a long isoform of VAB-3, comprising a Paired homology domain and a homeodomain, represses expression of ETS-5, a transcription factor required for expression of BAG fate. Repression of ets-5 requires the Eyes Absent homolog EYA-1 and the Six-class homeodomain protein CEH-32. We determined sequences that mediate high-affinity binding of ETS-5, VAB-3 and CEH-32. The ets-5 locus is enriched for ETS-5-binding sites but lacks sequences that bind VAB-3 and CEH-32, suggesting that these factors do not directly repress ets-5 expression. We propose that a promoter-selection system together with lineage-specific expression of accessory factors allows VAB-3/Pax6 to either promote or repress expression of specific cell fates in a context-dependent manner. This article has an associated 'The people behind the papers' interview.

Keywords: C. elegans; Chemosensory; Nervous system; VAB-3.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / metabolism
  • Bleomycin / metabolism
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Chlorambucil / metabolism
  • Cisplatin / metabolism
  • Cyclophosphamide / metabolism
  • Dactinomycin / metabolism
  • Gene Expression Regulation, Developmental / genetics
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Neurons / cytology
  • Neurons / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Promoter Regions, Genetic / genetics
  • Protein Tyrosine Phosphatases / genetics
  • Protein Tyrosine Phosphatases / metabolism
  • Proto-Oncogene Proteins c-ets / genetics
  • Proto-Oncogene Proteins c-ets / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Vinblastine / metabolism


  • Caenorhabditis elegans Proteins
  • ETS-5 protein, C elegans
  • Homeodomain Proteins
  • Intracellular Signaling Peptides and Proteins
  • Nuclear Proteins
  • Proto-Oncogene Proteins c-ets
  • Transcription Factors
  • ceh-32 protein, C elegans
  • vab-3 protein, C elegans
  • Bleomycin
  • Chlorambucil
  • Dactinomycin
  • Vinblastine
  • Cyclophosphamide
  • Protein Tyrosine Phosphatases
  • eya-1 protein, C elegans
  • Cisplatin

Supplementary concepts

  • VAB-III protocol